CN106536561A - 抗‑因子d抗体变体及其用途 - Google Patents
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Classifications
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- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/0012—Galenical forms characterised by the site of application
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
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- Molecular Biology (AREA)
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- Wood Science & Technology (AREA)
- Zoology (AREA)
- Urology & Nephrology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US201461987298P | 2014-05-01 | 2014-05-01 | |
| US61/987,298 | 2014-05-01 | ||
| US201462076372P | 2014-11-06 | 2014-11-06 | |
| US62/076,372 | 2014-11-06 | ||
| PCT/US2015/028641 WO2015168468A1 (fr) | 2014-05-01 | 2015-04-30 | Variants d'anticorps anti-facteur d et leurs utilisations |
Publications (1)
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| CN106536561A true CN106536561A (zh) | 2017-03-22 |
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| CN201580023643.0A Pending CN106536561A (zh) | 2014-05-01 | 2015-04-30 | 抗‑因子d抗体变体及其用途 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US10179821B2 (fr) |
| EP (1) | EP3137503A1 (fr) |
| JP (1) | JP2017515811A (fr) |
| KR (1) | KR20160147855A (fr) |
| CN (1) | CN106536561A (fr) |
| AU (1) | AU2015253042A1 (fr) |
| BR (1) | BR112016025312A2 (fr) |
| CA (1) | CA2944712A1 (fr) |
| CL (1) | CL2016002738A1 (fr) |
| CR (1) | CR20160561A (fr) |
| EA (1) | EA201692109A1 (fr) |
| IL (1) | IL248042A0 (fr) |
| MA (1) | MA39934A (fr) |
| MX (1) | MX2016014160A (fr) |
| PE (1) | PE20161440A1 (fr) |
| PH (1) | PH12016502015A1 (fr) |
| SG (1) | SG11201608868PA (fr) |
| TW (1) | TW201623337A (fr) |
| WO (1) | WO2015168468A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106905431A (zh) * | 2017-04-10 | 2017-06-30 | 旭华（上海）生物研发中心有限公司 | 抗人补体d因子的单克隆抗体及其用途 |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160042438A (ko) | 2013-08-12 | 2016-04-19 | 제넨테크, 인크. | 보체-연관 상태의 치료를 위한 조성물 및 방법 |
| US10179821B2 (en) | 2014-05-01 | 2019-01-15 | Genentech, Inc. | Anti-factor D antibodies |
| US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
| US10654932B2 (en) * | 2015-10-30 | 2020-05-19 | Genentech, Inc. | Anti-factor D antibody variant conjugates and uses thereof |
| WO2017075173A2 (fr) * | 2015-10-30 | 2017-05-04 | Genentech, Inc. | Anticorps et conjugués anti-facteur d |
| AU2016344133A1 (en) * | 2015-10-30 | 2018-05-17 | Genentech, Inc. | Anti-Factor D antibody formulations |
| IL290457B1 (en) | 2015-12-30 | 2024-10-01 | Kodiak Sciences Inc | Antibodies and their conjugates |
| JP2019506159A (ja) * | 2016-01-20 | 2019-03-07 | ヴィトリサ セラピューティクス， インコーポレイテッド | Ｄ因子を阻害するための組成物および方法 |
| CN107043422B (zh) * | 2016-01-28 | 2022-01-04 | 成都康弘生物科技有限公司 | 抗补体因子D的人源化Fab和人源化抗体及其用途 |
| WO2018136827A1 (fr) | 2017-01-20 | 2018-07-26 | Vitrisa Therapeutics, Inc. | Compositions à boucle en épingle à cheveux et procédés pour inhiber le facteur d |
| EA201991876A1 (ru) * | 2017-02-10 | 2020-03-13 | Дзе Трастиз Оф Дзе Юниверсити Оф Пенсильвания | Антитела против фактора d и их применения |
| WO2018191548A2 (fr) * | 2017-04-14 | 2018-10-18 | Kodiak Sciences Inc. | Anticorps antagonistes du facteur d du complément et leurs conjugués |
| CA3157509A1 (fr) | 2019-10-10 | 2021-04-15 | Kodiak Sciences Inc. | Procedes de traitement d'un trouble oculaire |
| CN115666578A (zh) | 2020-05-12 | 2023-01-31 | 阿雷克森制药公司 | 补体因子d抑制剂单独或结合抗c5抗体治疗阵发性睡眠性血红蛋白尿的用途 |
| EP4263600A1 (fr) | 2020-12-18 | 2023-10-25 | Century Therapeutics, Inc. | Systèmes récepteurs antigéniques chimériques ayant une spécificité de récepteur adaptable |
| EP4320149A1 (fr) * | 2021-04-09 | 2024-02-14 | Takeda Pharmaceutical Company Limited | Anticorps ciblant le facteur d du complément et leurs utilisations |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1260357C (zh) * | 1997-07-02 | 2006-06-21 | 基因技术股份有限公司 | 改进的抗lgE抗体以及改进多肽的方法 |
| CN101541345A (zh) * | 2006-09-25 | 2009-09-23 | 米迪缪尼有限公司 | 稳定化的抗体制剂和其应用 |
| CN101754980A (zh) * | 2007-05-23 | 2010-06-23 | 健泰科生物技术公司 | 补体相关眼疾的预防和治疗 |
| CN101796072A (zh) * | 2007-05-24 | 2010-08-04 | 埃博灵克斯股份有限公司 | 用于治疗骨疾病和病症的针对rank-l的氨基酸序列以及包括其的多肽 |
| WO2012031273A2 (fr) * | 2010-09-03 | 2012-03-08 | Stem Centrx, Inc. | Nouveaux modulateurs et leurs procédés d'utilisation |
| CN102665759A (zh) * | 2009-11-19 | 2012-09-12 | 默克雪兰诺有限公司 | 人源化抗il-22ra抗体 |
| CN102762227A (zh) * | 2009-09-30 | 2012-10-31 | 特雷康制药公司 | 内皮因子抗体 |
| TW201335183A (zh) * | 2011-12-28 | 2013-09-01 | Chugai Pharmaceutical Co Ltd | 人型化抗表皮調節素抗體及包含該抗體為有效成分之癌治療劑 |
| CN103619881A (zh) * | 2011-04-07 | 2014-03-05 | 安姆根有限公司 | 新的egfr结合蛋白 |
| CN103724433A (zh) * | 2008-04-28 | 2014-04-16 | 健泰科生物技术公司 | 人源化抗因子d抗体及其用途 |
Family Cites Families (140)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4741900A (en) | 1982-11-16 | 1988-05-03 | Cytogen Corporation | Antibody-metal ion complexes |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| GB8430252D0 (en) | 1984-11-30 | 1985-01-09 | Beecham Group Plc | Compounds |
| US5206344A (en) | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| ES2054667T3 (es) | 1986-04-28 | 1994-08-16 | Cetus Oncology Corp | Anticuerpos monoclonales contra c5a y des-arg74-c5a, su produccion y uso. |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5256642A (en) | 1988-04-01 | 1993-10-26 | The Johns Hopkins University | Compositions of soluble complement receptor 1 (CR1) and a thrombolytic agent, and the methods of use thereof |
| NZ230747A (en) | 1988-09-30 | 1992-05-26 | Bror Morein | Immunomodulating matrix comprising a complex of at least one lipid and at least one saponin; certain glycosylated triterpenoid saponins derived from quillaja saponaria molina |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| US5244800A (en) | 1990-04-27 | 1993-09-14 | The Uab Research Foundation | Crystals of human complement factor d that are triclinic |
| US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
| WO1992022653A1 (fr) | 1991-06-14 | 1992-12-23 | Genentech, Inc. | Procede de production d'anticorps humanises |
| AU2147192A (en) | 1991-06-28 | 1993-01-25 | Genentech Inc. | Method of stimulating immune response using growth hormone |
| US5587458A (en) | 1991-10-07 | 1996-12-24 | Aronex Pharmaceuticals, Inc. | Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof |
| CA2372813A1 (fr) | 1992-02-06 | 1993-08-19 | L.L. Houston | Proteine fixatrice biosynthetique pour marqueur du cancer |
| US5456909A (en) | 1992-08-07 | 1995-10-10 | T Cell Sciences, Inc. | Glycoform fractions of recombinant soluble complement receptor 1 (sCR1) having extended half-lives in vivo |
| JPH08500826A (ja) | 1992-08-21 | 1996-01-30 | ジェネンテク，インコーポレイテッド | Ｌｆａ−１仲介疾患を処置する方法 |
| AU6048294A (en) | 1992-11-25 | 1994-06-22 | Amgen Boulder Inc. | Modified insulin-like growth factors |
| US5861156A (en) | 1993-01-08 | 1999-01-19 | Creative Biomolecules | Methods of delivering agents to target cells |
| CN1134111A (zh) | 1993-04-07 | 1996-10-23 | 赛纳根公司 | 使用胰岛素样生长因子结合蛋白质的方法 |
| US5856300A (en) | 1994-05-12 | 1999-01-05 | T Cell Sciences, Inc. | Compositions comprising complement related proteins and carbohydrates, and methods for producing and using said compositions |
| US5679546A (en) | 1993-09-24 | 1997-10-21 | Cytomed, Inc. | Chimeric proteins which block complement activation |
| US5627264A (en) | 1994-03-03 | 1997-05-06 | Alexion Pharmaceuticals, Inc. | Chimeric complement inhibitor proteins |
| AU2191795A (en) | 1994-03-23 | 1995-10-09 | Alexion Pharmaceuticals, Inc. | Method for reducing immune and hemostatic dysfunctions during extracorporeal circulation |
| US5534615A (en) | 1994-04-25 | 1996-07-09 | Genentech, Inc. | Cardiac hypertrophy factor and uses therefor |
| US5919623A (en) | 1994-04-27 | 1999-07-06 | St. James's And Seacroft University Hospitals Nhs Trust | Nucleic acid mutation assays |
| US6074642A (en) | 1994-05-02 | 2000-06-13 | Alexion Pharmaceuticals, Inc. | Use of antibodies specific to human complement component C5 for the treatment of glomerulonephritis |
| US5679345A (en) | 1994-06-02 | 1997-10-21 | The Johns Hopkins University | Method for preventing complement-dependent rejection of organ or tissue transplants |
| WO2000053758A2 (fr) | 1999-03-08 | 2000-09-14 | Genentech, Inc. | Compositions et methodes de traitement des maladies immunitaires |
| US5679564A (en) | 1994-10-05 | 1997-10-21 | Antex Biologics, Inc. | Methods for producing enhanced antigenic campylobacter bacteria and vaccines |
| US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
| US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| AU718439B2 (en) | 1995-09-21 | 2000-04-13 | Genentech Inc. | Human growth hormone variants |
| US7122636B1 (en) | 1997-02-21 | 2006-10-17 | Genentech, Inc. | Antibody fragment-polymer conjugates and uses of same |
| WO2001036432A2 (fr) | 1999-11-19 | 2001-05-25 | Human Genome Sciences, Inc. | 18 proteines secretees humaines |
| US20050197285A1 (en) | 1997-03-07 | 2005-09-08 | Rosen Craig A. | Human secreted proteins |
| US6472520B2 (en) | 1997-03-21 | 2002-10-29 | The Trustees Of Columbia University In The City Of New York | Rat PEG-3 promoter |
| DK0973804T3 (da) | 1997-04-07 | 2007-05-07 | Genentech Inc | Anti-VEGF-antistoffer |
| US6884879B1 (en) | 1997-04-07 | 2005-04-26 | Genentech, Inc. | Anti-VEGF antibodies |
| ES2297889T3 (es) | 1997-07-14 | 2008-05-01 | Bolder Biotechnology, Inc. | Derivados de hormona de crecimiento y proteinas relacionadas. |
| ATE335511T1 (de) | 1997-08-26 | 2006-09-15 | Amgen Fremont Inc | Ein verfahren zur inhibierung der komplementaktivierung über einen alternativen weg |
| US6410708B1 (en) | 1997-11-21 | 2002-06-25 | Genentech, Inc. | Nucleic acids encoding A-33 related antigen polypeptides |
| US7282565B2 (en) | 1998-03-20 | 2007-10-16 | Genentech, Inc. | PRO362 polypeptides |
| US8088386B2 (en) | 1998-03-20 | 2012-01-03 | Genentech, Inc. | Treatment of complement-associated disorders |
| US7192589B2 (en) | 1998-09-16 | 2007-03-20 | Genentech, Inc. | Treatment of inflammatory disorders with STIgMA immunoadhesins |
| EP1481990B1 (fr) | 1997-11-21 | 2007-06-06 | Genentech, Inc. | Antigènes apparentés à A33 et leurs utilisations pharmacologiques |
| US8007798B2 (en) | 1997-11-21 | 2011-08-30 | Genentech, Inc. | Treatment of complement-associated disorders |
| US7419663B2 (en) | 1998-03-20 | 2008-09-02 | Genentech, Inc. | Treatment of complement-associated disorders |
| US7005504B2 (en) | 1998-01-22 | 2006-02-28 | Genentech, Inc. | Antibody fragment-peg conjugates |
| CA2320625A1 (fr) | 1998-02-09 | 1999-08-12 | Human Genome Sciences, Inc. | 45 proteines humaines secretees |
| US6956107B2 (en) | 1998-02-20 | 2005-10-18 | Tanox, Inc. | Inhibitors of complement activation |
| CA2321140C (fr) | 1998-02-20 | 2015-04-07 | Tanox, Inc. | Inhibiteurs de l'activation du complement |
| US7112327B2 (en) | 1998-02-20 | 2006-09-26 | Tanox, Inc. | Inhibition of complement activation |
| ES2312205T3 (es) | 1998-03-10 | 2009-02-16 | Genentech, Inc. | Nuevo polipeptido y acidos nucleicos que lo codifican. |
| JP2002523089A (ja) | 1998-08-27 | 2002-07-30 | インサイト・ファーマスーティカルズ・インコーポレイテッド | タンパク質輸送関連分子 |
| US6376653B1 (en) | 1998-09-28 | 2002-04-23 | Smithkline Beecham Plc | Tie2 antagonist antibodies |
| EP1141285A2 (fr) | 1998-12-16 | 2001-10-10 | Genentech, Inc. | Polypeptides secretes et transmembranaires et acides nucleiques codant pour ceux-ci |
| MXPA01006330A (es) | 1998-12-22 | 2002-07-02 | Genentech Inc | Metodos y composiciones para inhibir el crecimiento de celulas neoplasticas. |
| KR20060067983A (ko) | 1999-01-15 | 2006-06-20 | 제넨테크, 인크. | 효과기 기능이 변화된 폴리펩티드 변이체 |
| DE60045681D1 (de) | 1999-03-11 | 2011-04-14 | Merck Serono Sa | Vaskuläre adhesionsmoleküle und modulierung ihrer funktion |
| US6642353B1 (en) | 1999-03-17 | 2003-11-04 | Chugai Seiyaku Kabushiki Kaisha | Peptide ligands for the erythropoietin receptor |
| AU2883900A (en) | 1999-07-07 | 2001-01-30 | Genentech Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| CA2490909A1 (fr) | 1999-12-01 | 2001-06-07 | Genentech, Inc. | Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides |
| AU2001234962A1 (en) | 2000-02-10 | 2001-08-20 | Alexion Pharmaceuticals, Inc. | Mixtures of caspase inhibitors and complement inhibitors and methods of use thereof |
| US6821775B1 (en) | 2000-02-11 | 2004-11-23 | Genvec, Inc. | Viral vector encoding pigment epithelium-derived factor |
| AU2001249410A1 (en) | 2000-03-23 | 2001-10-03 | Tanox, Inc. | Anti-c2/c2a inhibitors of complement activation |
| ATE412185T1 (de) | 2000-04-29 | 2008-11-15 | Univ Iowa Res Found | Diagnostika und therapeutika für makula degeneration erkrankungen |
| EP1309620A2 (fr) | 2000-06-23 | 2003-05-14 | Genentech, Inc. | Compositions et procedes de diagnose et traitement de maladies faisant intervenir l'angiogenese |
| CA2416538A1 (fr) | 2000-07-20 | 2002-01-31 | Genentech, Inc. | Compositions et methodes diagnostiques et therapeutiques de troubles impliquant l'angiogenese |
| EP2113516B1 (fr) | 2000-10-10 | 2014-05-21 | Genentech, Inc. | Anticorps contre C5 inhibant l'activation de type II des cellules endothéliales |
| US6875432B2 (en) | 2000-10-12 | 2005-04-05 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
| CN1547590A (zh) | 2000-10-13 | 2004-11-17 | ¸ | 人源化抗-LT-β-R抗体 |
| KR100923514B1 (ko) | 2000-12-28 | 2009-10-27 | 알투스 파마슈티컬스 인코포레이티드 | 전항체 및 이의 단편의 결정과 이의 제조 및 사용 방법 |
| US20040077575A1 (en) | 2002-01-11 | 2004-04-22 | Giordano Giovan Giacomo | Inhibition of pathological angiogenesis in vivo |
| US6867189B2 (en) | 2001-07-26 | 2005-03-15 | Genset S.A. | Use of adipsin/complement factor D in the treatment of metabolic related disorders |
| US7432356B2 (en) | 2001-08-17 | 2008-10-07 | Genentech, Inc. | Complement pathway inhibitors binding to C5 and C5a without preventing formation of C5b |
| EP2348043A1 (fr) | 2001-10-02 | 2011-07-27 | Genentech, Inc. | Variantes du ligand APO-2 et leurs utilisations |
| EP2500032A1 (fr) | 2002-06-24 | 2012-09-19 | Genentech, Inc. | Variantes du ligand/Trail APO-2 et leurs utilisations |
| US20050180972A1 (en) | 2002-07-31 | 2005-08-18 | Wahl Alan F. | Anti-CD20 antibody-drug conjugates for the treatment of cancer and immune disorders |
| AR040778A1 (es) | 2002-08-06 | 2005-04-20 | Glaxo Group Ltd | Anticuerpos alterados o fragmentos funcionales que se unen a mag (glicoproteina asociada a mielina). |
| WO2004022594A2 (fr) | 2002-09-06 | 2004-03-18 | Cytos Biotechnology Ag | Methodes et composes d'immunomodulation |
| US7816497B2 (en) | 2002-10-30 | 2010-10-19 | University Of Kentucky | Compositions and methods for inhibiting drusen complement components C3a and C5a for the treatment of age-related macular degeneration |
| WO2004041160A2 (fr) | 2002-10-30 | 2004-05-21 | University Of Kentucky Research Foundation | Procedes et cobaye animal d'analyse de la degenerescence maculaire liee a l'age |
| US20060140939A1 (en) | 2003-02-21 | 2006-06-29 | Fung Sek C M | Methods for preventing and treating tissue damage associated with ischemia-reperfusion injury |
| RU2232991C1 (ru) | 2003-04-09 | 2004-07-20 | Государственное учреждение "Московский научно-исследовательский институт эпидемиологии и микробиологии им. Г.Н. Габричевского" | Способ определения функциональной активности фактора d комплемента человека |
| KR100512483B1 (ko) | 2003-05-07 | 2005-09-05 | 선바이오(주) | 신규한 폴리에틸렌글리콜-말레이미드 유도체의 합성방법 |
| US7709610B2 (en) | 2003-05-08 | 2010-05-04 | Facet Biotech Corporation | Therapeutic use of anti-CS1 antibodies |
| EP2267028A3 (fr) | 2003-06-30 | 2011-07-27 | Domantis Limited | Single domain anticorps (dAb) conjugés à PEG |
| WO2005014849A2 (fr) | 2003-07-03 | 2005-02-17 | Euro-Celtique, S.A. | Genes associes a des reponses a des douleurs neuropathiques |
| WO2005044853A2 (fr) | 2003-11-01 | 2005-05-19 | Genentech, Inc. | Anticorps anti-vegf |
| US20050106667A1 (en) | 2003-08-01 | 2005-05-19 | Genentech, Inc | Binding polypeptides with restricted diversity sequences |
| WO2005025509A2 (fr) | 2003-09-11 | 2005-03-24 | Board Of Regents, The University Of Texas System | Methodes et matieres de traitement de maladies et de troubles auto-immuns |
| US20050169921A1 (en) | 2004-02-03 | 2005-08-04 | Leonard Bell | Method of treating hemolytic disease |
| US7127355B2 (en) | 2004-03-05 | 2006-10-24 | Perlegen Sciences, Inc. | Methods for genetic analysis |
| US20090087854A1 (en) | 2007-09-27 | 2009-04-02 | Perlegen Sciences, Inc. | Methods for genetic analysis |
| US7794713B2 (en) | 2004-04-07 | 2010-09-14 | Lpath, Inc. | Compositions and methods for the treatment and prevention of hyperproliferative diseases |
| CA2580141C (fr) | 2004-09-23 | 2013-12-10 | Genentech, Inc. | Anticorps et conjugues produits avec de la cysteine |
| AU2005314461B2 (en) | 2004-11-18 | 2012-02-02 | The Rockefeller University | Methods and compositions for treating ocular disorders |
| WO2006071856A2 (fr) | 2004-12-23 | 2006-07-06 | Glycofi, Inc. | Immunoglobulines comprenant principalement une glycoforme man5glcnac2 |
| EP1833994A4 (fr) | 2005-01-04 | 2009-09-02 | Hitachi Chemical Co Ltd | Amplification en cercle roulant pour la production d'amorces |
| WO2006088950A2 (fr) | 2005-02-14 | 2006-08-24 | University Of Iowa Research Foundation | Procedes et reactifs pour le traitement et le diagnostic de la degenerescence maculaire liee a l'age |
| EP1907576B1 (fr) | 2005-06-08 | 2014-07-23 | University of Pittsburgh of the Commonwealth System of Higher Education | Gènes de prédisposition à une dégénérescence maculaire liée à l'âge (dmla) sur le chromosome 10q26 |
| PL1951279T3 (pl) | 2005-10-08 | 2017-12-29 | Apellis Pharmaceuticals, Inc. | Kompstatyna i jej analogi w zaburzeniach oczu |
| WO2007056227A2 (fr) | 2005-11-04 | 2007-05-18 | Genentech, Inc. | Utilisation d'inhibiteurs de la voie du complément pour traiter des maladies oculaires |
| US20070190057A1 (en) | 2006-01-23 | 2007-08-16 | Jian Wu | Methods for modulating mannose content of recombinant proteins |
| AR059066A1 (es) | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| US20080146501A1 (en) | 2006-02-13 | 2008-06-19 | University Of Iowa Research Foundation | Protective complement proteins and age-related macular degeneration |
| MX2008012617A (es) | 2006-03-31 | 2008-10-10 | Novartis Ag | Compuestos organicos. |
| CN101478949A (zh) | 2006-06-16 | 2009-07-08 | 瑞泽恩制药公司 | 适合玻璃体内施用的vegf拮抗剂的制剂 |
| US20100129379A1 (en) * | 2006-09-25 | 2010-05-27 | John Carpenter | Stabilized antibody formulations and uses thereof |
| EP2097455B1 (fr) | 2006-11-02 | 2014-10-22 | Genentech, Inc. | Anticorps anti facteur-d humanisés et leurs utilisations |
| US20090111708A1 (en) | 2007-05-11 | 2009-04-30 | Seddon Johanna M | Polynucleotides associated with age-related macular degeneration and methods for evaluating patient risk |
| US20090203001A1 (en) | 2007-08-24 | 2009-08-13 | The Regents Of The University Of Michigan | Compositions and methods for diagnosing and treating macular degeneration |
| AU2009251499B2 (en) | 2008-04-18 | 2015-07-16 | The General Hospital Corporation | Polymorphisms associated with age-related macular degeneration and methods for evaluating patient risk |
| US20110294682A1 (en) | 2008-04-28 | 2011-12-01 | The General Hospital Corporation | Polynucleotides Associated With Age-Related Macular Degeneration and Methods for Evaluating Patient Risks |
| ES2884117T3 (es) | 2008-06-25 | 2021-12-10 | Novartis Ag | Optimización de la solubilidad de inmunoaglutinantes |
| CN101724144A (zh) | 2008-11-03 | 2010-06-09 | 北京键凯科技有限公司 | 新型的多臂聚乙二醇及其制备方法和应用 |
| US20120003641A1 (en) | 2008-11-05 | 2012-01-05 | Graham Robert R | Genetic polymorphisms in age-related macular degeneration |
| WO2010075519A2 (fr) | 2008-12-23 | 2010-07-01 | Massachusetts Eye & Ear Infirmary | Variantes alléliques associées à la dégénérescence maculaire liée à l'âge avancée |
| CN102271632A (zh) | 2009-01-02 | 2011-12-07 | 爱尔康研究有限公司 | 可原位再填充的眼植入物 |
| WO2010085542A2 (fr) | 2009-01-23 | 2010-07-29 | Novartis Ag | Biomarqueurs associés à la dégénérescence maculaire liée à l'âge (dmla) |
| PL2391419T3 (pl) | 2009-01-29 | 2019-12-31 | Forsight Vision4, Inc. | Dostarczanie leku do tylnego odcinka |
| WO2010132459A2 (fr) | 2009-05-11 | 2010-11-18 | Cleveland Clinic Foundation | Biomarqueurs pour l'évaluation d'une dégénérescence maculaire liée à l'âge |
| CN102471783A (zh) | 2009-07-02 | 2012-05-23 | 新西兰郎泽科技公司 | 醇生产方法 |
| US8119348B2 (en) | 2009-07-10 | 2012-02-21 | The Regents Of The University Of Michigan | Compositions and methods for diagnosing and treating macular degeneration |
| WO2011017229A2 (fr) | 2009-08-06 | 2011-02-10 | Tufts - New England Medical Center | Composants de complément plasmatique en tant que marqueurs d'expression pour la dégénérescence maculaire liée à l'âge et les phénotypes afférents |
| US20110165648A1 (en) | 2009-11-04 | 2011-07-07 | Menno Van Lookeren Campagne | Co-crystal structure of factor D and anti-factor D antibody |
| RU2580038C2 (ru) | 2009-12-04 | 2016-04-10 | Дженентек, Инк. | Мультиспецифические антитела, аналоги антител, композиции и способы |
| CN103755949B (zh) | 2009-12-25 | 2016-04-13 | 天津键凯科技有限公司 | 多臂聚乙二醇衍生物及其与药物的结合物和凝胶 |
| EP2635704B1 (fr) | 2010-11-01 | 2017-04-19 | F. Hoffmann-La Roche AG | Prédiction de progression vers une dégénérescence maculaire liée à l'âge de stade avancé à l'aide de score polygénique |
| TW201321414A (zh) | 2011-10-14 | 2013-06-01 | Genentech Inc | 抗－ＨｔｒＡ１抗體及其使用方法 |
| JP6051998B2 (ja) | 2012-03-30 | 2016-12-27 | 日油株式会社 | マルチアーム型ポリエチレングリコール誘導体、その中間体及び製造方法 |
| KR20160042438A (ko) | 2013-08-12 | 2016-04-19 | 제넨테크, 인크. | 보체-연관 상태의 치료를 위한 조성물 및 방법 |
| EP3042205B1 (fr) * | 2013-09-06 | 2019-12-25 | F. Hoffmann-La Roche AG | Procédé visant à améliorer la stabilité d'un anticorps |
| US10179821B2 (en) | 2014-05-01 | 2019-01-15 | Genentech, Inc. | Anti-factor D antibodies |
-
2015
- 2015-04-30 US US14/700,853 patent/US10179821B2/en not_active Expired - Fee Related
- 2015-04-30 AU AU2015253042A patent/AU2015253042A1/en not_active Abandoned
- 2015-04-30 BR BR112016025312A patent/BR112016025312A2/pt not_active Application Discontinuation
- 2015-04-30 MX MX2016014160A patent/MX2016014160A/es unknown
- 2015-04-30 MA MA039934A patent/MA39934A/fr unknown
- 2015-04-30 EA EA201692109A patent/EA201692109A1/ru unknown
- 2015-04-30 CA CA2944712A patent/CA2944712A1/fr not_active Abandoned
- 2015-04-30 KR KR1020167032259A patent/KR20160147855A/ko unknown
- 2015-04-30 EP EP15721516.1A patent/EP3137503A1/fr not_active Withdrawn
- 2015-04-30 WO PCT/US2015/028641 patent/WO2015168468A1/fr active Application Filing
- 2015-04-30 JP JP2016564582A patent/JP2017515811A/ja active Pending
- 2015-04-30 TW TW104114014A patent/TW201623337A/zh unknown
- 2015-04-30 SG SG11201608868PA patent/SG11201608868PA/en unknown
- 2015-04-30 CR CR20160561A patent/CR20160561A/es unknown
- 2015-04-30 CN CN201580023643.0A patent/CN106536561A/zh active Pending
- 2015-04-30 PE PE2016002153A patent/PE20161440A1/es not_active Application Discontinuation
-
2016
- 2016-09-26 IL IL248042A patent/IL248042A0/en unknown
- 2016-10-10 PH PH12016502015A patent/PH12016502015A1/en unknown
- 2016-10-27 CL CL2016002738A patent/CL2016002738A1/es unknown
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1260357C (zh) * | 1997-07-02 | 2006-06-21 | 基因技术股份有限公司 | 改进的抗lgE抗体以及改进多肽的方法 |
| CN101541345A (zh) * | 2006-09-25 | 2009-09-23 | 米迪缪尼有限公司 | 稳定化的抗体制剂和其应用 |
| CN101754980A (zh) * | 2007-05-23 | 2010-06-23 | 健泰科生物技术公司 | 补体相关眼疾的预防和治疗 |
| CN101796072A (zh) * | 2007-05-24 | 2010-08-04 | 埃博灵克斯股份有限公司 | 用于治疗骨疾病和病症的针对rank-l的氨基酸序列以及包括其的多肽 |
| CN103724433A (zh) * | 2008-04-28 | 2014-04-16 | 健泰科生物技术公司 | 人源化抗因子d抗体及其用途 |
| CN102762227A (zh) * | 2009-09-30 | 2012-10-31 | 特雷康制药公司 | 内皮因子抗体 |
| CN102665759A (zh) * | 2009-11-19 | 2012-09-12 | 默克雪兰诺有限公司 | 人源化抗il-22ra抗体 |
| WO2012031273A2 (fr) * | 2010-09-03 | 2012-03-08 | Stem Centrx, Inc. | Nouveaux modulateurs et leurs procédés d'utilisation |
| CN103619881A (zh) * | 2011-04-07 | 2014-03-05 | 安姆根有限公司 | 新的egfr结合蛋白 |
| TW201335183A (zh) * | 2011-12-28 | 2013-09-01 | Chugai Pharmaceutical Co Ltd | 人型化抗表皮調節素抗體及包含該抗體為有效成分之癌治療劑 |
Non-Patent Citations (1)
| Title |
|---|
| HABERGER M 等: "Assessment of chemical modifications of sites in the CDRs of recombinant antibodies", 《MABS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106905431A (zh) * | 2017-04-10 | 2017-06-30 | 旭华（上海）生物研发中心有限公司 | 抗人补体d因子的单克隆抗体及其用途 |
| CN106905431B (zh) * | 2017-04-10 | 2020-01-17 | 旭华（上海）生物研发中心有限公司 | 抗人补体d因子的单克隆抗体及其用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| MA39934A (fr) | 2017-03-08 |
| US10179821B2 (en) | 2019-01-15 |
| CA2944712A1 (fr) | 2015-11-05 |
| EP3137503A1 (fr) | 2017-03-08 |
| MX2016014160A (es) | 2017-02-16 |
| JP2017515811A (ja) | 2017-06-15 |
| US20160017052A1 (en) | 2016-01-21 |
| AU2015253042A1 (en) | 2016-10-20 |
| WO2015168468A1 (fr) | 2015-11-05 |
| AU2015253042A2 (en) | 2016-10-27 |
| EA201692109A1 (ru) | 2017-03-31 |
| BR112016025312A2 (pt) | 2017-10-17 |
| TW201623337A (zh) | 2016-07-01 |
| PE20161440A1 (es) | 2017-01-26 |
| PH12016502015A1 (en) | 2017-01-16 |
| IL248042A0 (en) | 2016-11-30 |
| KR20160147855A (ko) | 2016-12-23 |
| SG11201608868PA (en) | 2016-11-29 |
| CL2016002738A1 (es) | 2017-06-23 |
| CR20160561A (es) | 2017-05-03 |
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